Xtandi (enzalutamide) Shows Long-Term Overall Survival in Metastatic Hormone-Sensitive Prostate Cancer - Astellas and Pfizer

Astellas Pharma Inc.  and Pfizer Inc.  announced longer-term follow-up results from an open-label extension of the Phase III ARCHES (NCT02677896) study, reporting a five-year follow up of overall survival (OS) benefits and a 30% reduction in the risk of death in men with metastatic hormone-sensitive prostate cancer (mHSPC) treated with Xtandi  (enzalutamide), an androgen receptor pathway inhibitor (ARPI), plus androgen deprivation therapy (ADT) compared to placebo plus ADT. These data will be presented during an oral presentation (Abstract #5005) at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Tuesday, June 3,)

About the ARCHES Study 
The Phase III, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,150 patients with metastatic hormone-sensitive prostate cancer (mHSPC) at sites in the United States, Canada, Europe, South America and the Asia-Pacific region. Patients in the ARCHES trial were randomized to receive Xtandi 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The ARCHES trial included patients with both low- and high-volume disease and both newly diagnosed patients with mHSPC and patients who had prior definitive therapy and subsequently developed metastatic disease. The trial also included some patients who had received recent treatment with docetaxel for mHSPC, but whose disease had not progressed. The primary endpoint of the trial was radiographic progression-free survival (rPFS), defined as the time from randomization to the first objective evidence of radiographic disease progression as assessed by central review, or death within 24 weeks of treatment discontinuation.

In addition to the key secondary endpoint of overall survival at final analysis, a post hoc 5-year analysis was executed with the intent to further quantify long-term overall survival at a clinically meaningful landmark follow-up of five years.

In patients with high-volume disease (HR: 0.70; 95% CI: 0.56-0.88) a 36-month improvement in median OS was observed. Additional clinically relevant subgroups of patients were evaluated, showing consistently improved survival: low-volume disease (HR: 0.71; 95% CI, 0.49-1.05); patients who had previously received docetaxel therapy (HR: 0.67; 95% CI, 0.43- 1.05) and those who had not received prior docetaxel therapy (HR: 0.71; 95% CI, 0.57-0.88). The incidence of treatment-emergent adverse events in the five-year follow-up is consistent with prior ARCHES analyses and no new safety signals were identified.

These results of the five-year follow-up from the ARCHES study will be submitted for publication in a peer-reviewed journal in the near future.

In addition to five-year data from the follow-up ARCHES study, eight-year data from the ENZAMET study assessing outcomes of enzalutamide versus non-steroidal anti-androgen (NSAA) – both plus testosterone suppression with or without docetaxel – in mHSPC will also be presented during a poster session at ASCO (Monday, June 2). This independent, Phase III trial sponsored by the University of Sydney (NCT02446405),  demonstrated a  reduction in risk of death in men with mHSPC.

ENZAMET (NCT02446405)  is a trial led by ANZUP Cancer Trials Group Limited in collaboration with the NHMRC (National Health and Medical Research Council) Clinical Trials Centre at the University of Sydney with trial sites in Australia, Canada, Ireland, New Zealand, UK and United States. The trial evaluates the potential of enzalutamide plus androgen deprivation therapy (ADT) versus a conventional non-steroidal anti androgen (NSAA) plus ADT in 1,125 men with mHSPC. The primary endpoint for the trial is overall survival (OS). 

With a median follow-up of 98 months, patients with mHSPC were treated with  Xtandi plus testosterone suppression or NSAA plus testosterone suppression, each group with or without docetaxel. The median OS in the  Xtandi group was 8.0 years and 5.8 years in the NSAA group (HR: 0.73; 95% CI, 0.63-0.86). OS at 96 months was 50% with  Xtandi and 40% for NSAA; progression-free survival (PFS) also favored  Xtandi over NSAA (HR: 0.49; 95% CI, 0.42-0.57). Prostate cancer accounted for 468 of all 622 deaths and were less frequent among those assigned Xtandi than NSAA (207 versus 261). Other causes accounted for a total of 154 deaths and were similarly frequent among those assigned Xtandi versus NSAA (78 versus 76). Mean duration of treatment was longer for Xtandi (58 months) than NSAA (36 months), with 33% remaining on Xtandi and 88% of these patients remained at the full dose of 160 mg.

Xtandi “The survival benefits of intervention with Xtandi in advanced prostate cancer are well-recognized,” added Shontelle Dodson, Executive Vice President, Head of Medical Affairs, Astellas. “The collective – and growing – body of data for Xtandi continues to reinforce its long-term efficacy and patient impact in prostate cancer, including in the metastatic setting, and shows that Xtandi is changing the trajectory of those living with the disease.”

“Until recently, patients with metastatic hormone-sensitive prostate cancer faced a poor prognosis, particularly in advanced stages, often due to treatment resistance,” said  Dr. Johanna Bendell,  Oncology Chief Development Officer, Pfizer. “As the only androgen receptor inhibitor demonstrating sustained five-year survival in this patient population, these data further reinforce Xtandi combined with androgen deprivation therapy as the standard-of-care for treating this advanced disease.”

"Historically, the likelihood of survival at five years for men with metastatic hormone-sensitive prostate cancer was low, but with advancements in initial treatment intensification like what we’ve seen with Xtandi, this is now becoming the standard,” said Dr. Andrew J. Armstrong,  Director of Research at the Center for Prostate & Urologic Cancers, Duke Cancer Institute, Durham, NC and ARCHES primary investigator. “In our five-year follow up of the global ARCHES trial, two-thirds of men are now surviving five years, representing a 13% absolute and 30% relative improvement over standard hormonal therapy alone, with benefits in patients with high and low disease burden that are meaningful to our patients.”

“Data from the eight-year follow-up of Xtandi are highly encouraging, as they show the progression-free survival and overall survival benefits are sustained out to at least eight years,” said Dr. Christopher Sweeney,  ANZUP Cancer Trials Group Limited, Sydney, Australia and ENZAMET follow-up primary investigator. “These results further support the value of Xtandi as a treatment regimen for metastatic hormone-sensitive prostate cancer.”